Myogenic regulation of arterial diameter: role of potassium channels with a focus on delayed rectifier potassium current

2005 ◽  
Vol 83 (8-9) ◽  
pp. 755-765 ◽  
Author(s):  
William C Cole ◽  
Tim T Chen ◽  
Odile Clément-Chomienne
Keyword(s):  
Potassium Channels ◽  
Molecular Mechanisms ◽  
Intraluminal Pressure ◽  
Delayed Rectifier ◽  
Resistance Arteries ◽  
Arterial Diameter ◽  
Resistance Vessels ◽  
Delayed Rectifier Potassium Current ◽  
Myogenic Regulation

The phenomenon of myogenic constriction of arterial resistance vessels in response to increased intraluminal pressure has been known for over 100 years, yet our understanding of the molecular mechanisms involved remains incomplete. The focus of this paper concerns the potassium (K+) channels that provide a negative feedback control of the myogenic depolarization of vascular smooth muscle cells that is provoked by elevations in intraluminal pressure, and specifically, the contribution of delayed rectifier (KDR) channels. Our knowledge of the important role played by KDR channels, as well as their molecular identity and acute modulation via changes in gating, has increased dramatically in recent years. Several lines of evidence point to a crucial contribution by heteromultimeric KV1 subunit-containing KDR channels in the control of arterial diameter and myogenic reactivity, but other members of the KV superfamily are also expressed by vascular myocytes, and less is known concerning their specific functions. The effect of pharmacological modulation of KDR channels is discussed, with particular reference to the actions of anorexinogens on KV1- and KV2-containing KDR channels. Finally, the need for a greater understanding of the mechanisms that control KDR channel gene expression is stressed in light of evidence indicating that there is a reduced expression of KDR channels in diseases associated with abnormal myogenic reactivity and vascular remodelling.Key words: resistance arteries, myogenic response, potassium channels, delayed rectifier K+ current, KV channels, KV1, KV2.

Abstract MP13: TRPM7 Downregulation Contributes To Cardiovascular Injury And Hypertension Induced By Aldosterone And Salt

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Francisco J Rios ◽  
ZhiGuo Zou ◽  
Karla B Neves ◽  
Sarah S Nichol ◽  
Livia L Camargo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Internal Diameter ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Vessel Structure ◽  
Cardiovascular Fibrosis ◽  
Fold Activation

TRPM7 has cation channel and kinase properties, is permeable to Mg 2+ , Ca 2+ , and Zn 2+ and is protective in the cardiovascular system. Hyperaldosteronism, which induces hypertension and cardiovascular fibrosis, is associated with Mg 2+ wasting. Here we questioned whether TRPM7 plays a role in aldosterone- induced hypertension and fibrosis and whether it influences cation regulation. Wild-type (WT) and TRPM7-deficient (M7+/Δ) mice were treated with aldosterone (600μg/Kg/day) and/or 1% NaCl (drinking water) (aldo, salt or aldo-salt) for 4 weeks. Blood pressure (BP) was evaluated by tail-cuff. Vessel structure was assessed by pressure myography. Molecular mechanisms were investigated in cardiac fibroblasts (CF) from WT and M7+/Δ mice. Protein expression was assessed by western-blot and histology. M7+/Δ mice exhibited reduced TRPM7 expression (30%) and phosphorylation (62%), levels that were recapitulated in WT aldo-salt mice. M7+/Δ exhibited increased BP by aldo, salt and aldo-salt (135-140mmHg) vs M7+/Δ-veh (117mmHg) (p<0.05), whereas in WT, BP was increased only by aldo-salt (134mmHg). Mesenteric resistance arteries from WT aldo-salt exhibited increased wall/lumen ratio (80%) and reduced internal diameter (15%) whereas vessels from M7+/Δ exhibited thinner walls by reducing cross-sectional area (35%) and increased internal diameter (23%) after aldo-salt. Aldo-salt induced greater collagen deposition in hearts (68%), kidneys (126%) and aortas (45%) from M7+/Δ vs WT. Hearts from M7+/Δ veh exhibited increased TGFβ, IL-11 and IL-6 (1.9-fold), p-Smad3 and p-Stat1 (1.5-fold) whereas in WT these effects were only found after aldo-salt. Cardiac expression of protein phosphatase magnesium-dependent 1A (PPM1A), a Mg 2+ -dependent phosphatase, was reduced (3-fold) only in M7+/Δ mice. M7+/Δ CF showed reduced proliferation (30%) and PPM1A (4-fold) and increased expression of TGFβ, IL-11 and IL-6 (2-3-fold), activation of Stat1 (2-fold), Smad3 (9-fold) and ERK1/2 (8-fold) compared with WT. Mg 2+ supplementation normalized cell proliferation and reduced protein phosphorylation in M7+/Δ CF (p<0.05). Our findings indicate a protective role of TRPM7 in aldosterone-salt induced cardiovascular injury through Mg 2+ -dependent mechanisms.

Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries

1999 ◽  
Vol 277 (4) ◽  
pp. H1546-H1552 ◽  
Author(s):  
Cornel J. M. Kerkhof ◽  
Erik N. T. P. Bakker ◽  
Pieter Sipkema
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
No Production ◽  
Cremaster Muscle ◽  
Resistance Arteries ◽  
Arterial Diameter ◽  
Spontaneous Tone ◽  
Cytochrome P 450

The role of arachidonic acid metabolism and nitric oxide (NO) in hypoxia-induced changes of vascular tone was investigated in first-order cannulated rat cremaster muscle resistance arteries. Spontaneous tone reduced arterial diameter from 179 ± 2 μm (fully dilated) to 98 ± 3 μm under normoxia ([Formula: see text] = 150 mmHg). Hypoxia ([Formula: see text] 5–10 mmHg) had no significant effect on arterial diameter under conditions of spontaneous tone. The effect of hypoxia was not changed after blockade of cyclooxygenase with indomethacin or after blockade of lipoxygenase with nordihydroguaiaretic acid. However, after partial blockade of cytochrome P-450 4A enzymes with 17-octadecynoic acid (17-ODYA), hypoxia increased the diameter by 65 ± 6 μm ( P < 0.05). This increase could be inhibited by N G-nitro-l-arginine (l-NNA) or 20-hydroxyeicosatetraenoic acid (20-HETE). 17-ODYA induced a concentration-dependent dilation under normoxia, which could be blocked by endothelium removal orl-NNA. 17-ODYA did not increase smooth muscle sensitivity to NO. We conclude that, under conditions of spontaneous tone and in the absence of luminal flow, hypoxia (5–10 mmHg) has no effect on the diameter of resistance arteries from the rat cremaster muscle. Inhibition of the cytochrome P-450 4A pathway of arachidonic acid metabolism under normoxia induces NO production by the endothelium. Hypoxia induces an NO-mediated dilation when cytochrome P-450 4A enzymes are partially inhibited.

scholarly journals Pathophysiology of Vascular Remodeling in Hypertension

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Nicolás F. Renna ◽  
Natalia de las Heras ◽  
Roberto M. Miatello
Keyword(s):  
Vascular Remodeling ◽  
Potential Role ◽  
Independent Predictor ◽  
Resistance Arteries ◽  
Historical Aspects ◽  
Animal Data ◽  
Resistance Vessels ◽  
Basic Concepts ◽  
The Impact

Vascular remodeling refers to alterations in the structure of resistance vessels contributing to elevated systemic vascular resistance in hypertension. We start with some historical aspects, underscoring the importance of Glagov’s contribution. We then move to some basic concepts on the biomechanics of blood vessels and explain the definitions proposed by Mulvany for specific forms of remodeling, especially inward eutrophic and inward hypertrophic. The available evidence for the existence of remodeled resistance vessels in hypertension comes next, with relatively more weight given to human, in comparison with animal data. Mechanisms are discussed. The impact of antihypertensive drug treatment on remodeling is described, again with emphasis on human data. Some details are given on the three mechanisms to date which point to remodeling resistance arteries as an independent predictor of cardiovascular risk in hypertensive patients. We terminate by considering the potential role of remodeling in the pathogenesis of endorgan damage and in the perpetuation of hypertension.

Role of Delayed Rectifier Potassium Channels in Cardiac Repolarization and Arrhythmias

Physiology ◽  
1997 ◽  
Vol 12 (4) ◽  
pp. 152-157 ◽  
Author(s):  
MC Sanguinetti ◽  
MT Keating
Keyword(s):  
Potassium Channels ◽  
Action Potentials ◽  
Ventricular Arrhythmias ◽  
Gene Mutations ◽  
Delayed Rectifier ◽  
Cardiac Repolarization ◽  
Cardiac Action ◽  
Life Threatening ◽  
Slow Onset

Cardiac action potentials are long because the magnitude of some potassium currents is reduced at depolarized potentials. The slow onset of repolarization is initiated by the opening of delayed rectifier potassium channels. A decrease in function of these channels resulting from gene mutations or pharmacological block increases risk of life-threatening ventricular arrhythmias.

06 Possible role of the ultra-rapid delayed rectifier potassium current (IKur) in action potential repolarisation in rabbit heart

Heart ◽  
2010 ◽  
Vol 97 (1) ◽  
pp. e2-e2
Author(s):  
Y. Cui ◽  
C. Wilson ◽  
S. Turner ◽  
S. Graham ◽  
N. McMahon ◽  
...  
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Rabbit Heart ◽  
Delayed Rectifier ◽  
Delayed Rectifier Potassium Current

Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aurelie Nguyen Dinh Cat ◽  
Tayze T Antunes ◽  
Glaucia E Callera ◽  
Augusto C Montezano ◽  
Ying He ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptors ◽  
Resistance Arteries ◽  
Brown Adipose

Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.

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